It is used to treat
heart block and episodes of
Adams–Stokes syndrome that are not caused by
ventricular tachycardia or fibrillation, in emergencies for
cardiac arrest until electric shock can be administered, for bronchospasm occurring during anesthesia, and as an adjunct in the treatment of
hypovolemic shock,
septic shock, low cardiac output (hypoperfusion) states, congestive heart failure, and cardiogenic shock.[2] It is also used to prevent
Torsades de Pointes in patients with
long QT refractory to magnesium and to treat patients with intermittent Torsades de Pointes refractory to treatment with magnesium.[3]
Historically, it was used to treat asthma via metered aerosol or nebulizing devices; it was also available in sublingual, oral, intravenous, and intramuscular formulations.[4] The U.S. National Asthma Education and Prevention Program Expert Panel recommends against its use as a nebulizer for acute bronchoconstriction.[5]
Isoprenaline can also ameliorate the impairment of intestinal stem cells mediated by β2-adrenoreceptors after chemotherapy.[6]
Contraindications
It should not be used in people with tachyarrhythmias (except in special circumstances),[7] tachycardia or heart block caused by digitalis poisoning, ventricular arrhythmias which require inotropic therapy, or with
angina.[2]
Adverse effects
Adverse effects of isoprenaline include nervousness, headache, dizziness, nausea, visual blurring, tachycardia,
palpitations, angina, Adams-Stokes attacks,
pulmonary edema,
hypertension,
hypotension, ventricular arrhythmias, tachyarrhythmias, difficulty breathing, sweating, mild tremors, weakness, flushing, and
pallor.[2] Isoproterenol has been reported to cause insulin resistance leading to diabetic ketoacidosis.[8]
Pharmacology
The adverse effects of isoprenaline are also related to the drug's cardiovascular effects. Isoprenaline can produce
tachycardia (an elevated
heart rate), which predisposes people who take it to
cardiac arrhythmias.[4]
Pharmacodynamics
Isoprenaline is a
β1 and
β2 adrenoreceptor agonist and has almost no activity on
alpha adrenergic receptors at low levels.[4] However, at higher concentrations, isoprenaline can evoke α-AR-mediated responses.[9][10] Its agonist effects at
TAAR1 provide it with pharmacodynamic effects that resemble those of the endogenous
trace amines, like
tyramine.[11]
Isoprenaline's effects on the
cardiovascular system (non-selective) relate to its actions on cardiac β1 receptors and β2 receptors on smooth muscle within the
tunica media of
arterioles. Isoprenaline has positive inotropic and
chronotropic effects on the heart. β2 adrenoceptor stimulation in arteriolar smooth muscle induces vasodilation. Its inotropic and chronotropic effects elevate
systolicblood pressure, while its vasodilatory effects tend to lower
diastolic blood pressure. The overall effect is to decrease
mean arterial pressure due to the β2 receptors' vasodilation.[12]
The
isopropylamine group in isoprenaline makes it selective for β receptors. The free
catecholhydroxyl groups keep it susceptible to enzymatic metabolism.[13]
Pharmacokinetics
The plasma half-life for isoproterenol is approximately two to five minutes. It is degraded enzymatically via catechol O-methyltransferase (COMT) primarily in the liver and excreted in the urine as sulfated conjugates.[14][15]
It was first approved in the US in 1947.[4]
Between 1963 and 1968 in England, Wales, Scotland, Ireland, Australia, and New Zealand there was an increase in deaths among people using isoprenaline to treat asthma. This was attributed to overdose: the inhalers produced in that area were dispensing five times the dosage dispensed by inhalers produced in the US and Canada, where the deaths were not observed.[16][17]
Society and culture
Brands
Isoprenaline is marketed under many brand names worldwide, including Aleudrina, Asthpul, Iludrin, Isomenyl, Isuprel, Neo-Epinine, Neodrenal, Proternol, and Saventrine.[1] It is also marketed as a
combination drug with
cromoglicic acid as Frenal Compositum, in combination with
pronase as Isopal P, and in combination with
atropine as Stmerin D.[1]
^Jalba MS (2008). "Three generations of ongoing controversies concerning the use of short acting beta-agonist therapy in asthma: a review". The Journal of Asthma. 45 (1): 9–18.
doi:
10.1080/02770900701495512.
PMID18259990.
S2CID31732029.
† References for all endogenous human TAAR1 ligands are provided at
List of trace amines
‡ References for synthetic TAAR1 agonists can be found at
TAAR1 or in the associated compound articles. For TAAR2 and TAAR5 agonists and inverse agonists, see
TAAR for references.